: Several pieces of evidence suggest a strong association between human immunodeficiency virus (HIV) infection and M. tuberculosis (Mtb). In particular, data from the investigator and that of others suggest that co-infection of cells with mycobacteria and HIV results in increased HIV replication. The purpose of this proposal is to investigate the impact of Mtb on HIV activation in alveolar macrophages (AM), lymphocytes, and human pulmonary arteriolar endothelial cell (HPAE), and to elucidate the underlying mechanisms. The following specific aim are designed to investigate the hypothesis that Mtb infection enhances HIV replication in lung. Aim 1: To explore the effect of Mtb on HIV replication in AM and HPAE, including cells from normal donors infected with either/both pathogens in vitro as well as cells from HIV and Mtb infected donors. AIM 2: To study the effect of Mtb on lymphocyte activation and HIV replication. AIM 3: To measure the induction of cytokines and their role in Mtb-mediated HIV enhancement. AIM 4: To determine whether HIV transcription is modulated by Mtb and whether Mtb induces cellular transcription factors such as Nfkb which may affect HIV replication. AIM 5: To examine the role of cell-cell contact between HIV and Mtb infected AM, HPAE and lymphocytes; in particular they will examine the role of ICAM-1 in this process.